Posaconazole (CAS registry number: 171228-49-2, CAS name: 2,5-anhydro-1,3,4-trideoxy-2-C-(2,4-difluorophenyl)-4-[[4-[4-[4-[1-[(1S,2S)-1-ethyl-2-hydroxypropyl]-1,5-dihydro-5-oxo-4H-1,2,4-triazol-4-yl]phenyl]-1-piperazinyl]phenoxy]methyl]-1-(1H-1,2,4-triazol-1-yl)-D-threo-pentitol) which is represented by the following chemical structure (I)
is a triazole antifungal agent available as an oral suspension (40 mg/mL) under the tradename Noxafil®.
WO 95/17407 A1 and WO 96/38443 A1 disclose the compound having the chemical structure (I) and its use in treating fungal infections.
WO 2010/000668 A1 discloses crystalline form IV of posaconazole and pharmaceutical compositions comprising the same. In addition methods of preparing crystalline form IV of posaconazole are disclosed.
WO 2011/144653 A1 (page 51, lines 17-27) discloses that posaconazole form IV is obtained by the solvent-mediated solid state transformation process according to WO 2010/000668 A1 and a concrete example for the preparation of form IV is given in example 6 of WO 2011/144653 A1.
However, the processes described in WO 2010/000668 A1 have the drawbacks of long and inconsistent solvent-mediated solid state transformation times. Hence, there is a need for an optimized process for the preparation of crystalline form IV of posaconazole with reduced and constant transformation times in order to increase the operational capacity and to reduce production costs on large scale.